Mitomycin C(1) is a clinically useful antineoplastic antibiotic compound. The mechanism of action of this medicinal agent is poorly understood. Knowledge of the correct chemical pathway leading to the activation and subsequent reaction of this compound may provide the molecular basis for subsequent research in cancer chemotherapy and permit general drug design to proceed on a less empirical basis. In this proposal, a novel mechanism is offered for the reaction of all mitomycins in vitro and in vivo. Experiments have been suggested to substantiate these hypotheses as well as to gain information concerning the energetics of key steps. The use of bifunctional nucleophiles are promoted as unique diagnostic aids in these mechanistic studies. A select series of modified mitomycins are also proposed as potential candidates for future pharmacological evaluation. Emphasis has been placed on the development of new mitomycin-based substrates which have increased selectivity and decreased toxicity. This project summary contained formulas, drawings, tables or nonkeyable data which are not shown above.